The present invention is concerned with novel substituted 3-cyanothiophene acetamides, their manufacture and their use as medicaments. The present invention further relates to pharmaceutically acceptable salts of these 3-cyanothiophene compounds and pharmaceutical compositions containing these compounds.
The glucagon receptor (GLUR) is a G-protein coupled 7-transmembrane domain receptor (GPCR) of the secretin family. When the natural hormonal ligand glucagon binds to the GLUR, there is an activation of adenylate cyclase and a concomitant increase in cAMP production. This increase in cAMP causes an activation of glycogen phosphorylase resulting in an increase in hepatic glucose production. The actions of glucagon are counter-regulatory to insulin and thus it is believed to play a central role in glucose homeostasis. Glucagon has been used clinically to rescue diabetic patients from hypoglycemia. Thus, a small molecule GLUR antagonists has considerable potential for the treatment of diabetes.